title: Global coagulation in myeloproliferative neoplasms.
abstract: In spite of their recognized risk of thrombosis, patients with myeloproliferative neoplasms (MPN) show little or no abnormalities of traditional coagulation tests, perhaps because these are unable to represent the balance between pro- and anticoagulants nor the effect of platelets and blood cells. We investigated whether global tests such as thrombin generation in platelet-rich plasma (PRP) or thromboelastometry in whole blood were able to detect signs of procoagulant imbalance in MPN. The endogenous thrombin potential (ETP) of 111 patients and 89 controls was measured in PRP with platelet count adjusted to the original patient- or control-count. Testing was performed with and without thrombomodulin (the physiological protein C activator) and results were expressed as ETP ratios (with/without thrombomodulin). High ETP ratios reflect resistance to thrombomodulin and were taken as indexes of procoagulant imbalance. Patients were also investigated by thromboelastometry that provides such parameters as the clot formation time (CFT) and maximal clot firmness (MCF). Short CFT or high MCF were taken as indexes of procoagulant imbalance. ETP ratios were higher in patients than in controls and were directly correlated with platelet counts and inversely with the plasma levels of free protein S, protein C and antithrombin. Patients on hydroxyurea had lower ETP ratios than those on other treatments. CFT was shorter and MCF was greater in patients than controls; CFT and MCF were correlated with platelet counts. In conclusion, patients with MPN display a procoagulant imbalance detectable by thrombin generation and thromboelastometry. These tests might be useful in the frame of clinical trials to assess their association with the occurrence of thrombosis and with the effect of therapeutic strategies in MPN.
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via Pace 9, 20122, Milan, Italy, armando.tripodi@unimi.it.
authors.forename: Armando
authors.initials: A
authors.lastname: Tripodi
authors.forename: Veena
authors.initials: V
authors.lastname: Chantarangkul
authors.forename: Francesca
authors.initials: F
authors.lastname: Gianniello
authors.forename: Marigrazia
authors.initials: M
authors.lastname: Clerici
authors.forename: Laura
authors.initials: L
authors.lastname: Lemma
authors.forename: Lidia
authors.initials: L
authors.lastname: Padovan
authors.forename: Loredana
authors.initials: L
authors.lastname: Gatti
authors.forename: Pier Mannuccio
authors.initials: PM
authors.lastname: Mannucci
authors.forename: Flora
authors.initials: F
authors.lastname: Peyvandi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001777:Blood Coagulation / Q000502:physiology*; D001780:Blood Coagulation Tests / Q000379:methods; D019046:Bone Marrow Neoplasms / Q000097:blood* / Q000175:diagnosis; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000097:blood* / Q000175:diagnosis; D053657:Platelet-Rich Plasma / Q000378:metabolism; D011087:Polycythemia Vera / Q000097:blood / Q000175:diagnosis; D013916:Thrombelastography / Q000379:methods; D013917:Thrombin / Q000378:metabolism*
chemical_list: D013917:Thrombin